tbuckley/cabot-search huggingface dataset:
Estimated cost of adverse event (AE) management for patients (pts) with metastatic renal cell carcinoma (mRCC) treated with a VEGFR TKI.
Authors: Jeffrey Thomas Yorio, Aviva G. Asnis-Alibozek, Vijay Kasturi, Thomas E. Hutson
Journal: Journal of Clinical Oncology (2023)

629 Background: Nearly all mRCC pts will be treated with one or more VEGFR TKI, alone or in combination with an immunotherapy (IO) or mTOR-inhibitor, during their therapeutic journey and may experience associated AEs. Evidence from the tivozanib (tivo) TIVO-3 trial suggests that median duration of clinically relevant VEGFR TKI class effect AEs is ≤90 days (range 14-90). Cost of AE management has not been clearly quantified to date. This study aimed to estimate how differences in TKI AE profile may impact treatment cost efficiency, particularly in later line (3L+) settings. Methods: iKnowMed EMR was used to identify mRCC pts from USON or Onmark Network, with matched 3 rd party insurance claims, that initiated VEGFR TKI treatment between Jan 2015 and Mar 2021. First occurrence of each VEGFR TKI class effect AE was indexed, and associated costs for 90-day (longest median AE duration) follow-up was captured. To assess burden across different TKIs, average per-patient AE management cost was calculated using incidence data from trials supporting FDA approvals, and weight-adjusted to estimated number of commercially insured 3L/4L pts in a 1,000,000-member plan. Results: 5,958 mRCC pts were identified, of which 4,464 were on at least one TKI regimen. Among those, 1,777 experienced an index AE; 1,072 successfully matched to claims data [median 69 years (range 25-94); 55% ECOG PS 0/1; 69% male], accounting for 1,667 unique index AE cases. Most were on cabozantinib (cabo), axitinib (axi), or pazopanib; lenvatinib (len), sunitinib (sun), and sorafenib were also represented. &gt;80% were TKI only, with the rest TKI+IO (18%) or TKI+mTOR (6%). AE costs largely originated from outpatient visits (range 38-77%), excluding renal failure (58% inpatient). Mean cost per AE ranged from $76 (proteinuria) to $1,687 (mucositis/stomatitis). Overall, estimated costs of managing VEGFR TKI class effect AEs in 3L/4L showed lowest resource burden with tivo, and highest with len+everolimus (len+ev; Table). Conclusions: Average VEGFR TKI AE management costs derived from real-world mRCC pts demonstrated differences in healthcare resource burden, with overall anticipated cost dependent on TKI regimen utilized. [Table: see text]
Patient experiences with tissue-based genomic testing during active surveillance for prostate cancer.
Authors: Michael Leapman, Ryan Andrew Sutherland, Cary Philip Gross, Xiaomei Ma, Farah Jeong, Tyler M Seibert, Matthew R. Cooperberg, William Catalona, Stacy Loeb, Dena Schulman-Green
Journal: Journal of Clinical Oncology (2023)

333 Background: Tissue-based gene expression (genomic) tests improve estimates of prostate cancer aggressiveness and are increasingly used for patients considering or engaged in active surveillance; however, little is known about patient experiences with genomic testing and its role in decision-making for active surveillance. Methods: We performed a qualitative descriptive study consisting of in-depth, semi-structured interviews of patients with low- or favorable-intermediate-risk prostate cancer managed with active surveillance. The interview guide focused on experiences with biopsy-based genomic testing during their decision-making for prostate cancer management. We used purposive sampling to include patients who received genomic testing as part of routine clinical care and we over-sampled Black and Latino men. We continued interviews until thematic saturation was reached, iteratively created a code key and used conventional content data analysis. Results: The mean age was 68 years (range 51-79; n=20). At initial biopsy, 17 (85%) had a Gleason grade group 1, and 3 (15%) had a grade group 2 tumor. Fourteen (70%) participants identified their race/ethnicity as White, 5 (25%) as Black, and 2 (10%) as Latino. The decision to undergo genomic testing was driven by both participants and physicians’ recommendations; however, some participants were unaware that testing had occurred. Overall, participants understood the role of genomic testing in estimating their prostate cancer risk, and the test results increased their confidence in the decision for active surveillance. However, participants did not understand the difference between tissue-based gene expression tests and germline genetic tests, and commonly believed that tissue-based tests measured hereditary cancer risk. While some participants expressed satisfaction with the explanations provided by their physicians, others felt that communication was inaccessible and lacked sufficient detail. Conclusions: Patients interact with and are influenced by the results of biopsy-based genomic testing during active surveillance for prostate cancer, however testing may increase informational needs. Our findings indicate areas for improvement in patient counseling that can be used to increase patient knowledge and comfort with genomic testing.
Comparison of costs incurred by patients treated with adjuvant nivolumab versus placebo for high-risk muscle-invasive urothelial carcinoma.
Authors: Xin Yin, Shreya Mitra, Miraj Y Patel, Sandip Ranjan, Hitesh Bhandari, Ravi Potluri, Lisa Rosenblatt
Journal: Journal of Clinical Oncology (2023)

500 Background: The global, phase 3 CheckMate 274 trial showed significant and clinically meaningful benefit of adjuvant nivolumab (NIVO) treatment versus placebo (PBO) in reducing risk of disease recurrence or death in patients with muscle-invasive urothelial carcinoma (MIUC) at a high risk of recurrence after radical cystectomy. The implications of these benefits on costs associated with the treatment are unknown. Here, we estimate and compare per-patient medical and subsequent therapy costs in the United States for patients with high-risk MIUC initiating treatment with adjuvant NIVO or PBO. Methods: This analysis used individual data from all randomized patients for healthcare resources utilized (HCRU) from the CheckMate 274 trial. Medical (inpatient, lab, office visits, procedures, concomitant drugs) and subsequent treatment (surgery, radiotherapy, systemic therapy) resources were included, while the costs of NIVO were not included. US-based unit costs were applied to these resources and were obtained from Healthcare Cost and Utilization Project, Micromedex RED BOOK, and CMS databases, supplemented by inputs from published literature. HCRU was only captured on 2 follow-up visits after discontinuation of study therapy: follow-up 1 occurred approximately 35 days after the last dose or coinciding with the date of discontinuation, and follow-up 2 occurred approximately 80 days after follow-up 1. To align with data captured at follow-up visits, HCRU and related costs were analyzed from randomization to 12 months and 16 months. Costs were adjusted for censoring using the Kaplan–Meier sampling average estimator. Results: Total per-patient costs incurred by the NIVO-treated cohort (n = 353) were 6% lower than the PBO cohort (n = 356) over the 12-month period from randomization ($36K vs $38K) and 13% lower over the 16-month period from randomization ($41K vs $47K) (Table). The NIVO cohort, compared with placebo, had lower subsequent treatment costs ($2K vs $11K over 12 months, and $3K vs $18K over 16 months) despite higher medical costs ($34K vs $27K over 12 months, and $37K vs $29K over 16 months). Conclusions: Patients treated with adjuvant NIVO incurred lower total costs versus PBO, with the differential increasing over time. The slightly higher medical costs incurred by the NIVO cohort were offset by the substantially lower subsequent therapy costs. [Table: see text]
Survival outcomes of metastasis-directed therapy for solitary sites of metastatic clear cell renal cell carcinoma.
Authors: Akeem Ronell Lewis, Christine M. Lohse, Timothy D. Lyon, John Cheville, Bradley C. Leibovich, Vidit Sharma, Brian Addis Costello
Journal: Journal of Clinical Oncology (2023)

674 Background: Metastasis directed therapy (MDT) is associated with improved cancer-specific survival and delay in use of systemic therapy for metastatic clear cell RCC (mccRCC). Although the benefits of MDT may differ based on organ site of metastasis due to differences in disease biology, survival based on site of metastasis remain underexplored. We aim to evaluate survival outcomes of patients who underwent MDT for solitary sites of mccRCC. Methods: The Mayo Clinic Nephrectomy Registry was queried to identify adults undergoing radical or partial nephrectomy for unilateral, sporadic ccRCC from 2000 to 2019 with a single site of metastasis treated with MDT including complete metastasectomy or radiation, in lieu of systemic therapy. Overall and cancer-specific survival were estimated using the Kaplan-Meier method, with the duration of follow-up calculated from the date of metastasis to the date of death or last follow-up. Associations with time to death from RCC were evaluated using Cox proportional hazards regression models and summarized with hazard ratios and 95% confidence intervals (CIs). Results: In this cohort of 207 mccRCC patients, 152 underwent complete metastasectomy and 55 underwent radiation. 133 died at a median of 2.7 years (IQR 1.2-4.7) following metastasis, including 105 who died from RCC at a median of 2.2 years (IQR 1.0-3.9). The median duration of follow-up for the 74 patients who were still alive at last follow-up was 8.1 years (IQR 3.7-12.1). Overall survival rates (95% CI) at 2, 4, 6, 8, and 10 years following metastasis were 73% (69-79), 54% (48-62), 45% (38-52), 37% (30-44), and 32% (26-40), respectively; cancer-specific survival rates were 75% (69-81), 56% (50-64), 47% (41-55), 44% (37-52), and 42% (35-50), respectively. Age, poor performance status, presence of synchronous metastasis and asynchronous metastasis &lt;1 year from nephrectomy, tumor size, and bone metastasis were associated with death from RCC (table). Conclusions: These findings provide useful survival benchmarks to patients who are considering MDT as a therapeutic option. In addition, synchronous and asynchronous metastasis &lt;1 year from nephrectomy, poor performance status, and bone metastasis are significantly associated with worse survival from mccRCC. [Table: see text]
Positron emission tomography of patients with confirmed prostate cancer using <sup>64</sup>Cu-SAR-bisPSMA.
Authors: Louise Emmett, Veronica Wong, Nat Lenzo, Eva Lengyelova, Colin Biggin
Journal: Journal of Clinical Oncology (2023)

318 Background: Prostate cancer (PC) is the second most frequent malignancy in men worldwide. 68 Ga-PSMA-11 is one of the most widely used radiotracers for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with PC and is part of standard clinical practice at many centres. Due to the longer half-life and shorter positron range of copper-64 (t 1/2 =12.7 hours; mean positron range=0.56 mm), a novel PSMA-targeting radiotracer labelled with this radionuclide, 64 Cu-SAR-bisPSMA, has the potential to provide advantages over 68 Ga-PSMA-11 (t 1/2 =68 minutes; mean positron range=3.5 mm). The 12.7 hour half-life of Cu-64 allows the central manufacturing of 64 Cu-SAR-bisPSMA with a product shelf-life of up to 2 days. The longer half-life enables PET imaging from 1 to 72 hours after administration which offers greater flexibility in terms of scheduling of patients and may translate into detection of additional lesions due to increased Standardized Uptake Values (SUV) in the lesions relative to background following biological clearance of the tracer from organs over time. The shorter positron range may lead to improved resolution on the scan and thus, better detection of small lesions, including those that are in close proximity to each other, or to organs involved in clearance of the product such as the bladder and kidneys. In addition to the potential imaging and supply benefits of Cu-64, current generation PSMA targeting agents such as 68 Ga-PSMA-11 have only a single targeting functional group. 64 Cu-SAR-bisPSMA has two PSMA-targeting functional groups, which can lead to improved tumor uptake and retention. This was shown in a preclinical study, where 64 Cu-SAR-bisPSMA outperformed the monomeric 64 Cu-SAR-PSMA with respect to both tumor uptake and retention (Zia et al, 2019). Methods: Patients with untreated, histopathology-proven, intermediate- to high-risk PC, planned for radical prostatectomy underwent 68 Ga-PSMA-11 PET/CT per institutional practice and were subsequently allocated to 1 out of 3 dose cohorts (1:1:3) to receive either 100 MBq, 150 MBq or 200 MBq of 64 Cu-SAR-bisPSMA, respectively. A PET/CT was acquired at 3-hours (±1 hour) post-injection of 64 Cu-SAR-bisPSMA. Two independent, blinded, central readers assessed the detection of primary PC on the 200 MBq 64 Cu-SAR-bisPSMA PET/CTs as the primary endpoint. To compare the intensity of lesions on 68 Ga-PSMA-11 and 64 Cu-SAR-bisPSMA PET, both readers determined the SUVs (SUVmax, SUVmean) and tumour-to-background ratio (ratio of lesion SUVmax and background SUVmean) in up to 5 concordant lesions between 68 Ga-PSMA-11 and 64 Cu-SAR-bisPSMA PET/CT as an exploratory endpoint. Clinical trial information: NCT04839367 .
Comparison of ctDNA between African American and Caucasian patients with CRPC post abiraterone and/or enzalutamide.
Authors: Albert Jang, Minqi Huang, Crystal Casado, Sydney Caputo, Patrick L Sweeney, Sree M Lanka, Kanika Gupta, Olivia Pocha, Nicholas Habibian, Maddie Hawkins, Alexandra Lieberman, Jennifer Schwartz, Ellen B. Jaeger, Patrick Miller, Jodi Lyn Layton, Pedro C. Barata, Brian E. Lewis, Elisa M. Ledet, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2023)

35 Background: Genetic differences between African American and Caucasian patients with advanced prostate cancer may contribute to racial disparities in terms of treatment outcomes and survival, hence further exploration is warranted. We assessed ctDNA differences between African American and Caucasian men in the setting of CRPC post treatment with abiraterone and/or enzalutamide. Methods: From 2015 through 2022 at Tulane Cancer Center, 250 patients with CRPC including 50 African Americans and 200 Caucasian with prior abiraterone and/or enzalutamide treatment were included. All patients had ctDNA assessed via Guardant360. Data including both gene mutations and types of mutations were for between 73-80 genes. Clinical annotation including initial staging, treatment history, and genetic testing were obtained. Statistical analyses included Fisher’s exact test and Wilcoxon rank-sum test. Results: The most common pathogenic/likely pathogenic (P/LP) alterations in both African Americans and Caucasians were TP53 (44% and 46%, respectively), AR (50% and 39%), and PIK3CA (14% and 9%). CDK12 (OR= 8.955, 95% C.I. [2.156, 37.192], p=0.003) and KIT (OR= 5.710, 95% C.I. [1.235, 26.397]. p=0.031) alterations were more frequently detected in African Americans. In terms of pathologic mutation type, frameshift mutations were significantly more frequent in African Americans (OR= 2.293, 95% C.I. [1.103, 4.769], p=0.035). All patients were CRPC at the time of testing and had prior abiraterone and/or enzalutamide, but there were no significant differences between African American and Caucasian patients with regards to prior life-extending therapies. Conclusions: African Americans with CRPC post treatment with abiraterone and/or enzalutamide had a higher frequency of P/LP CDK12 and KIT mutations, which have both been shown to lead to aggressive clinical features and treatment resistance. African Americans also had a higher incidence of frameshift mutations, a finding not previously noted. [Table: see text]
Does the time-of-day administration of immune checkpoint inhibitors affect efficacy in patients with metastatic renal cell carcinoma? A single-center study.
Authors: Laia Fernandez-Mañas, Laura Gonzalez Aguado, Caterina Aversa, Laura Ferrer-Mileo, Marta Garcia de Herreros, Natalia Jiménez, Albert Febrer, Roger Vernet, Samuel García-Esteve, Begona Mellado, Oscar Reig Torras
Journal: Journal of Clinical Oncology (2023)

681 Background: Immune checkpoint inhibitors (ICI) are the standard of care for metastatic renal cell carcinoma (mRCC). Circadian rhythm drives organisms to properly predict and react to cyclical changes in the environment, and also affects the adaptive immune response. Here, we study the relationship between time-of-day ICI administration and outcomes in mRCC patients (pts). Methods: This is a single-center retrospective study of ICI-treated mRCC pts diagnosed from January 2014 to March 2022. Day and time of each ICI infusion (inf) for each pt were obtained from the pharmacy records. Proportion of ICI inf administered after 4:30 pm (ICI430) was calculated based on a prior publication (Quian, Lancet Oncol 2021). The primary outcome was overall survival (OS), and secondary endpoints were time on treatment (TOT), time to next treatment (TNT), and overall response rate (ORR). The proportion of ICI430 as a continuous variable, and the dichotomized data (≥20% and ≥50%) were correlated with OS, TOT and TNT by Kaplan-Meier analysis and Cox regression, and with ORR by logistic regression. Results: Overall, 104 pts and 1763 inf were analyzed (Table). 48 pts were treated with 1st line (1L) ICI. 903 inf were administered (median 12 inf per pt, 1 - 111), 146 (15.6%) after 4:30 pm. 12 (25%) and 2 (4.2%) pts received ≥ 20% and ≥ 50% ICI430. Due to the small number of events (5 deaths and 15 progressions), of ICI430, and heterogeneity of treatments in 1L, we focus on pts treated with 2nd line (2L) ICI. 56 pts were treated with ICI in ≥2L. 860 inf were administered (median 8 inf per pt, 1 - 123), 180 (20.9%) after 4:30 pm. 15 (34.1%) and 9 (20.5%) pts received ≥20% and ≥50% ICI430. Pts who received ≥20% after 4:30pm, received fewer inf (7 vs. 16, p=0.022), had a worse TOT (4.3 vs. 9 m, HR 2.5, p=0.013), a trend to a worse TNT (6.3 vs. 10.5 m, HR 1.9, p=0.06) and a worse OS (16.9 vs. 56.1 m, HR 3.1, p=0.01). Similar results were obtained when using ≥ 50% ICI430 as the cut-off (TOT, 2 vs. 9m, p=0.007; TNT 4.7 vs. 10.5m, p=0.05; OS 16.9 vs. 36.6m, p=0.1), as well as higher frequency of progressive disease (85.7 vs. 21.9%, p=0.006). A significant association with OS (HR 1.02, p=0.03) was shown when analyzing ICI430 as a continuous variable, meaning a 16% increase in the risk of death for each 10% increment of ICI inf after 4:30 pm. Conclusions: Administration of ≥2L ICI after 4:30 pm is associated with poor overall survival. Our results could have a direct impact on pt survival and organization of outpatient clinics, but further research is needed. [Table: see text]
TROPHU-U-01 cohort 5: Evaluation of maintenance sacituzumab govitecan (SG) plus zimberelimab (ZIM), ZIM, or avelumab in cisplatin-eligible patients (pts) with unresectable or metastatic urothelial cancer (mUC).
Authors: Thomas Powles, Andrea Necchi, Ignacio Duran, Yohann Loriot, Chethan Ramamurthy, Alejandro Recio-Boiles, Randy F. Sweis, Jens Bedke, Julia Tonelli, Mitch Sierecki, Petros Grivas, Philippe Barthelemy
Journal: Journal of Clinical Oncology (2023)

TPS598 Background: SG is an antibody-drug conjugate composed of an anti-trophoblast cell-surface antigen-2 (Trop-2) antibody coupled to a topoisomerase-I inhibitor, SN-38, via a hydrolyzable linker. In Cohort 1 of the phase 2 TROPHY-U-01 trial, SG monotherapy resulted in a 27% objective response rate (ORR) and median overall survival (OS) of 10.9 months with an overall manageable toxicity profile in pts with locally advanced or mUC who previously received platinum-based therapy and a checkpoint inhibitor (CPI; Tagawa S, et al. J Clin Oncol. 2021). These results led to accelerated FDA approval of SG in this population. The CPI ZIM is a fully human IgG4 monoclonal antibody targeting PD-1. CPIs are active in mUC, including avelumab that is FDA-approved as switch maintenance therapy for locally advanced or mUC that has not progressed with first-line platinum-based chemotherapy. Cohort 5 of the TROPHY-U-01 trial will evaluate the safety, tolerability, and efficacy of SG + ZIM vs ZIM alone vs avelumab as switch maintenance in pts with mUC who have received gemcitabine (GEM)/cisplatin without progressive disease (PD). Methods: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, global, phase 2 trial. Cohort 5 includes pts who have not progressed after completion of 4-6 cycles of GEM/cisplatin. Key eligibility requirements include ≥18 y; ECOG PS 0-1; available tissue for biomarker testing; adequate blood counts without transfusion or growth factor within 2 weeks of study drug initiation; creatinine clearance ≥30 mL/min. A safety lead-in of 6-8 pts will be conducted, where pts will be treated with SG 10 mg/kg IV on D1 and D8 of a 21-D cycle plus ZIM 360 mg IV q3wk on a 21-D cycle. On safety lead-in, if SG + ZIM is deemed safe, pts will be randomized 1:1:1. Those in Arm 1 will receive SG 10 mg/kg IV on D1 and D8 of a 21-D cycle followed by ZIM 360 mg IV, q3wk (D1 of a 21-D cycle). Pts in Arm 2 will receive avelumab 800 mg IV q2wk (D1 of a 14-D cycle). Pts in Arm 3 will receive ZIM 360 mg IV q3wk. All pts will continue treatment until PD, unacceptable toxicity, or loss of clinical benefit. The primary endpoint is progression-free survival based on central review by RECIST 1.1 criteria. Secondary endpoints include OS (all arms), safety/tolerability of SG in combination with ZIM (Arm 1). Cohort 5 aims to enroll an estimated 158 pts. A sample size of 50 pts per randomized arm is determined based on clinical consideration for exploring the activity of anticancer agents. Clinical trial information: NCT03547973 .
Main reasons of choice of formulation and route of triptorelin treatment initiated in patients with prostate cancer (PCa): TALISMAN study.
Authors: Antoine Thiery-Vuillemin, Gilles Crehange, Thierry Lebret, Nathalie Pello Leprince Ringuet, Valérie Perrot, Jerome Rigaud
Journal: Journal of Clinical Oncology (2023)

104 Background: Modalities of use of androgen deprivation therapy (ADT), like triptorelin, in real life, at the era of new strategies in advanced stages, lack of recent data. Our purpose here was to describe main reasons of choice of formulation and route (F&amp;R) of triptorelin treatment (Tt) declared by the physician. Patient comorbidities, cancer aggressiveness and physician habits may influence their choices. Methods: Initiated in 2020, a prospective, multicenter, non-interventional study is ongoing in France (TALISMAN, NCT04593420). Patients with histologically confirmed PCa, eligible for ≥ 12-month triptorelin Tt within its label were enrolled. Interim analysis of baseline data was planned when 50% of 786 planned patients were enrolled. Modalities of use, including F&amp;R of triptorelin prescribed [monthly intramuscular (1mIM), every 3 months subcutaneous (3mSC) or intramuscular (3mIM), every 6 months intramuscular (6mIM)], were described. Results: 509 patients were included in the interim analysis. Overall population was presented at ASCO-GU22. Subgroups of F&amp;R are presented here. Main F&amp;R prescribed was 3mSC (70.7%). Main baseline parameters in F&amp;R subgroups are presented (except for 1mIM, 4 patients (0.8%)). 31 patients had missing F&amp;R data and were not included in subgroups. 62.1% of patients overall received at least one concomitant systemic Tt for comorbidity at baseline (58.2% in 3mIM, 61.7% in 3mSC and 6mIM). 18.6% and 13.0% of patients overall received, respectively, platelet aggregation inhibitor and anticoagulant; they were 20.9% and 13.8% in 3mSC, 7.3% and 5.5% in 3mIM, 18.5% and 11.1% in 6mIM. Conclusions: Main reason of choice of F&amp;R of triptorelin was physician preferred F&amp;R (47.7%); noticeable reasons included anticoagulants for the choice of 3mSC, planned total duration of Tt for 3mIM and 6mIM, and potential impact on compliance for 6mIM. As the covid pandemic may change the management of patients with prostate cancer, longer acting formulations may become more attractive. Clinical trial information: NCT04593420 . [Table: see text]